The objective of this research program is a detailed elucidation of mechanism and transition state structure in enzyme catalyzed redox reactions. Our investigations for the coming year will be focused on the copper-containing enzyme dopamine-beta-hydroxylase from bovine adrenal glands. Specific goals include (1) the measurement of secondary isotope effects under conditions where the magnitude of experimental primary isotope effects approximate a recently estimated "intrinsic" primary deuterium isotope effect of 9.4; (2) the investigation of structure-reactivity correlations for the hydroxylation of a series of ring substituted phenethylamines in an effort to establish the relative contribution of electronic, steric and hydrophobic parameters to substrate binding and turnover; (3) cross-linking of soluble and reconstituted membrane-bound enzyme in an effort to probe changes in oligomeric structure upon integration of enzyme into a lipid bilayer and (4) further kinetic and chemical characterization of the inhibition of dopamine-beta-hydroxylase by a new class of suicide reagents.